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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2806-2814.
Prepublished online as a Blood First Edition Paper on December 19, 2006; DOI 10.1182/blood-2006-06-030213.
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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Expression and release of soluble HLA-E is an immunoregulatory feature of endothelial cell activation
Stéphanie Coupel1,
Anne Moreau2,
Mohamed Hamidou3,
Vaclav Horejsi4,
Jean-Paul Soulillou1, and
Béatrice Charreau1
1 Institut National de la Santé et de la Recherche Médicale, Unit 643, Institut de Transplantation et de Recherche en Transplantation, Nantes, France;
2 Service d'Anatomo-Pathologie, Centre Hospitalo-Universitaire (CHU) Hôtel-Dieu, Nantes, France;
3 Service de Médecine Interne, CHU Hôtel-Dieu, Nantes, France;
4 Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Human leukocyte antigen (HLA)E belongs, with HLA-G and HLA-F, to the nonclassic major histocompatibility complex (MHC) class I (Ib) molecules, broadly defined by a limited polymorphism and a restricted pattern of cellular expression. In contrast to HLA-G, the expression and function of HLA-E and HLA-F in physiologic and pathologic processes remain poorly established. In the present study, we show that HLA-E protein expression in normal human nonlymphoid organs is mainly restricted to endothelial cells (ECs). HLA-E is also basally expressed by B and T lymphocytes, natural killer (NK) cells and by macrophages. We demonstrate that tumor necrosis factor (TNF ), interleukin-1ß (IL-1ß), and interferon (IFN ) up-regulate the cell-surface expression of HLA-E on ECs in vitro and induce the release of soluble HLA-E (sHLA-E). HLA-E up-regulation protects IFN -activated ECs from NK-mediated cell lysis, while sHLA-E protects bystander cells. Finally, sHLA-E is not detected in normal sera, and increased serum levels correlate with disease activity in patients with antineutrophil cytoplasmic antibodyassociated systemic vasculitis. Thus, HLA-E expression and release of sHLA-E are features of EC activation and emphasize immunoregulatory functions of the endothelium. The present identification of soluble HLA-E molecules may have important implications in understanding the pathogenesis of immune-mediated vascular diseases and for the diagnosis and monitoring of patients.

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